Optical imaging of MMP expression and cancer progression in an inflammation-induced colon cancer model

• Published in: International journal of cancer Vol. 131; no. 8; pp. 1846 - 1853
• Main Authors: Lee, Chang-Moon, Jang, DooRye, Cheong, Su-Jin, Jeong, Min-Hee, Kim, Eun-Mi, Kim, Dong Wook, Lim, Seok Tae, Sohn, Myung-Hee, Jeong, Hwan-Jeong
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-10-2012; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: Animals; Azoxymethane - toxicity; beta catenin; beta Catenin - metabolism; Biological and medical sciences; Blotting, Western; Cancer; cancer diagnosis; Carbocyanines; Carcinogens - toxicity; Colonic Neoplasms - chemically induced; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal cancer; Dextran Sulfate - toxicity; Diagnostic Imaging; Disease Models, Animal; Disease Progression; fluorescent peptide; Gastroenterology. Liver. Pancreas. Abdomen; Immunoenzyme Techniques; Inflammation - chemically induced; Inflammation - metabolism; Inflammation - pathology; Male; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; matrix metalloproteinases; Medical imaging; Medical research; Medical sciences; Mice; Mice, Inbred BALB C; Molecular weight; optical imaging; Peptide Fragments - pharmacology; Peptides; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Rectal disease; beta catenin; Peptides; Colorectal cancer; Metalloendopeptidases; Beta; Colon cancer; Cancerology; Dicotyledones; Angiospermae; Tumor progression; Intestinal disease; Diagnosis; Catenin; matrix metalloproteinases; fluorescent peptide; Enzyme; Optical imaging; cancer diagnosis; Inflammation; Malignant tumor; Chenopodiaceae; Colonic disease; Peptidases; Hydrolases; Digestive diseases; Spermatophyta; Models; Cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.27451

The purpose of this study was to use a near‐infrared (NIR) fluorescent cyclic His‐Try‐Gly‐Phe peptide to characterize and image the expressions of matrix metalloproteinases (MMPs), which are correlated with cancer promotion, in an inflammation‐induced colorectal cancer (ICRC) model. We explored the relationship between the development of colon cancer and the expression of MMPs at the same colonic sites in ICRC models. To develop ICRC models, mice were administered a single intraperitoneal dose (10 mg/kg) of azoxymethane (AOM) and exposed orally to 2% dextran sodium sulfate (DSS) for one week. MMP‐2 expression and β‐catenin activation in colonic lesions were characterized by immunohistochemical (IHC) staining. After being treated with inducers for some time, cancerous lesions were found to express high β‐catenin and MMP‐2. The profiles of MMP expression were correlated with β‐catenin activation in the colonic lesions. c(KAHWGFTLD)NH2 (C6) peptide was prepared by standard Fmoc peptide synthesis to target MMPs. Molecular weight of Cy5.5‐C6 was 1,954.78 g/mol (calculated MW = 1955.23 g/mol). The in vitro characterization of Cy5.5‐C6 showed MMP binding specificity in a cell experiment. In vivo NIRF imaging showed high accumulation of Cy5.5‐C6 in tumors with associated expression of MMP‐2 in colonic lesions after intravenous injection. The MMP‐2 specificity of Cy5.5‐C6 was confirmed by successful inhibition of probe uptake in the tumor due to the presence of excess C6 peptide. The use of Cy5.5‐C6 to target MMP‐2 has the potential to be developed into an effective molecular imaging agent to monitor ICRC progress.